Jason Weatherald, University of Calgary
Supervisor: Todd Anderson, University of Calgary
Pulmonary arterial hypertension (PAH) is a chronic fatal disease characterized by progressive elevation in pulmonary arterial pressure, right ventricular (RV) failure, and ultimately, death. The mechanisms leading to RV failure and are not well defined, but may be relate to reflected waves that increase RV afterload and RV work. Wave intensity analysis (WIA) is a method of characterizing waves and wave reflection in the pulmonary circulation with a time-domain analysis of pressure and flow. The reservoir-wave approach (RWA) resolves arterial pressure and flow into their volume-related and wave-related components. After subtracting the volume- related pressure and flow from the measured values, WIA is used to characterize waves. By initially eliminating the volume-related component, RWA permits a more sensitive characterization of wave-related events in the pulmonary circulation. Significant recent advances in 4D MRI-based flow quantification and 4D RV strain analysis also now provide unique opportunities to study related changes in PA flow and RV loading and RV work.
We will prospectively evaluate 10 patients with PAH with right heart catheterization, echocardiography and 4- D cardiac magnetic resonance (CMR) to permit simultaneous RWA-based measurements. Following baseline measurements, we will examine the influence of inhaled nitric oxide (iNO) on these parameters. Using 4D MRI-based flow quantification, 4D RV strain analysis will be performed, allowing the study of related changes in pulmonary arterial flow, wave reflection, RV loading and work. We are uniquely positioned to do the latter work through strategic partnership with the Stephenson Cardiac Imaging Centre, which has developed expertise in these techniques. As such, we aim to perform a combined validation study of RWA using simultaneous 4D MRI techniques both at rest and following pulmonary vasodilation with iNO.
Through the CVN-Bayer Research Fellowship, this innovative multidisciplinary project will establish a new research partnership between the Libin Cardiovascular Institute, Stephenson Cardiac Imaging Centre, and the Southern Alberta Pulmonary Hypertension Clinic, and cultivate an early physician-researcher career. This project provides a tremendous opportunity for Dr. Weatherald to lead an independent research project and advance his research skills under the mentorship of Dr. Todd Anderson and Dr. John Tyberg. Following completion of this project and demonstrating RWA feasibility in PAH, we plan to pursue further studies of WIA and 4-D RV strain techniques to characterize other pulmonary vascular disease states, such as chronic thromboembolic pulmonary hypertension (CTEPH), valvular heart disease and left ventricular dysfunction. It is currently unknown whether WIA and 4-D RV Strain analysis will improve diagnosis or prognostication in PAH, though we aim to evaluate this question in future studies. In particular, as WIA can estimate of distance to wave reflection site, it may be able to discriminate between reflection site in CTEPH versus PAH, and between proximal versus distal obstruction in patients with CTEPH. This could have significant clinical utility in the diagnosis and management of these patients.